title: Long-acting injectable antiretrovirals for HIV treatment and prevention.
abstract: OBJECTIVE
  Long-acting antiretroviral (ARV) drugs may improve adherence to therapy and extend opportunities for therapeutic or prophylactic intervention to underserved patient populations. This review focuses on recent advances in the development of small molecule long-acting injectable ARV agents.
  
  
  RESULTS
  The need for combination ART and physicochemical and dosing limitations of current ARV drugs impede attempts to redevelop them as long-acting injectable formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand transfer inhibitor, have enabled crystalline nanoparticle formulations to progress to clinical trials.
  
  
  CONCLUSIONS
  Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. Complementary pharmacologic properties of both agents - different mechanisms of action, resistance profiles, metabolic pathways, lack of drug interactions and low daily oral doses - offer the potential for combination use. Phase I studies of the pharmacokinetics and safety of each long-acting formulation alone and in combination indicate that a monthly dosing regimen is possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic suppression; results will inform future studies using the injectable formulations. Additional preclinical and clinical studies indicate a potential use of each agent for HIV pre-exposure prophylaxis.
authors.affiliation: aGlaxoSmithKline, Research Triangle Park, North Carolina bViiV Healthcare, Philadelphia, Pennsylvania, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Spreen
authors.forename: David A
authors.initials: DA
authors.lastname: Margolis
authors.forename: John C
authors.initials: JC
authors.lastname: Pottage
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D007267:Injections; D009570:Nitriles / Q000493:pharmacokinetics / Q000627:therapeutic use; D011728:Pyridones / Q000493:pharmacokinetics / Q000627:therapeutic use; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068696:Rilpivirine; D054659:Diketopiperazines
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D009570:Nitriles; D011728:Pyridones; D011743:Pyrimidines; D000068696:Rilpivirine; C584914:cabotegravir; D054659:Diketopiperazines